Topical formulation for pain relief

ABSTRACT

Described herein are topical pain compositions comprising between 15 and 90% mannitol, for use in the treatment of pain, itch and other cutaneous nerve conditions. The resulting compositions may be in the form of creams, gels, lotions, ointments, foams, suppositories, and sprays.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a non-provisional application taking priority fromU.S. patent application Ser. No. 61/816,913, filed Apr. 29, 2013, thedisclosure of which is hereby incorporated by reference.

FIELD

This invention relates to the field of topical formulations for painrelief, and more particularly to mannitol-based topical formulations forconditions in which cutaneous nerves may be involved.

BACKGROUND

Oral pain relievers are typically prescribed for treatment of acute andchronic pain, including arthritic pain, musculoskeletal pain, andneuropathic pain. Oral pain relievers often have side effects, some ofwhich can be severe. Topical pain relievers work locally and are lesslikely to cause severe systemic side effects. Some topical painrelievers include non-steroidal anti-inflammatory drugs (NSAIDs),salicylates, lidocaine, capsaicin, amitriptyline, glyceryl trinitrate,opioids, menthol, and gabapentin.

Research suggests that NSAIDs are most effective as topical painrelievers for a number of conditions including joint-related conditions;however, they may not be suitable for all subjects experiencing pain,due to allergies, drug intolerances or contraindications such as renalfailure, hypertension or gastric ulcers from absorption of topicalNSAIDs.

Some other topical pain relievers are classified as counterirritants,such as menthol, capsaicin and camphor, which work by creating a burningor cooling sensation that distracts the person from the actual pain.Capsaicin in particular causes undesirable side effects includingburning and stinging.

There is a need for alternative topical pain relievers with minimal sideeffects, and without unpleasant localized cooling and burningsensations.

Mannitol is a sugar alcohol with the formula C₆H₈(OH)₆. It reducesintracellular water retention and also has free radical scavengingproperties. Mannitol's most common uses are related to its function asan osmotic diuretic, thereby making it a suitable agent for treatingkidney failure, reducing swelling in the brain and eye, and treatingcystic fibrosis. Mannitol is also used as a sweetener in chewing gum andfor diabetics.

Mannitol has been shown to be effective in pain management when injectedunder the skin or intravenously. For example, intravenous mannitolreduces neuro-inflammation by reducing edema. In addition, injection ofmannitol just under the skin is used to treat neuropathic pain. Finally,dental anaesthesia is more effective when mannitol is included with thestandard nerve block agents, lidocaine and epinephrine.

Mannitol has been used for treating pain intravenously andsubcutaneously, but never topically.

SUMMARY

In one embodiment, the invention is a topical pain relief compositioncomprising mannitol and at least one excipient.

In another embodiment, the present is a topical pain relief compositioncomprising between 15 and 90% mannitol by weight in a mixture comprisingpropylene glycol, purified water, isopropyl palmitate, caprylic/caprictriglyceride, ceteareth 20, cetearyl alcohol, glyceryl stearate, PEG-100stearate, dimethicone, octyldodecanol, lecithin, ethylhexylglycerin, andphenoxyethanol.

In yet another embodiment, the present is a use of a topical compositioncomprising between 15 and 90% mannitol by weight for topically treatingpain, itch and other conditions involving cutaneous nerves.

DETAILED DESCRIPTION

A new route of administration for mannitol for the specific indicationof pain is disclosed. The topical composition allows for transdermaldelivery of mannitol. This specific composition produces a cosmeticallyelegant product that enables mannitol to be readily absorbed through theskin providing relief of pain within seconds to minutes. In sometesting, pain relief has shown to last anywhere from two hours to up to48 hours. No adverse effects from the use of the cream have beenreported. The ingredients, including mannitol, are typically classifiedas natural health products.

Mannitol is mixed with one or more suitable excipients to maximizetransdermal delivery. In some embodiments, mannitol is incorporated intoa cream, gel, lotion, ointment, foam, suppository, or a spray, usingmethods known in the art. Suitable excipients include emulsifiers,organogelators and emollients. Emulsifiers include polyethylene glycolstearate, a glycol stearate, a glyceryl stearate, cetearyl alcohol andceteareth 20, methylcellulose, Cetomacrogol 1000, and lecithin. Suitableorganogelators include 4-tertbutyl-1-aryl cyclohecanols derivatives,polymeric (e.g. poly(ethylene glycol), polycarbonate, polyesters, andpoly(alkylene), Gemini gelators (e.g. N-lauroyl-L-lysine ethyl ester),Boc-Ala(1)-Aib(2)-β-Ala(3)-OMe (synthetic tripeptide), and low molecularweight gelators (e.g. fatty acids and n-alkanes). Suitable emollientsinclude cetostearyl alcohol, cetyl alcohol, isopropyl palmitate,caprylic/capric triglyceride, PPG-2 myristyl ether propionate,dimethicone, methicone, petrolatum, lanolin, and mineral oil.

If desired, other additives including surfactants, penetrationenhancers, preservatives, viscosity modifiers, and emulsion stabilizersmay be included in the mannitol compositions. Suitable surfactantsinclude sodium lauryl sulfate, cetostearyl alcohol, ceteareth 12,ceteareth 20, cetearyl alcohol, Cetomacrogol 1000, stearic acid, andpoloxamer. Suitable penetration enhancers include propylene glycol.Suitable preservatives include methylparaben, propylparaben,ethylhexylglycerin, phenoxyethanol, chlorocresol, potassium sorbate,sorbic acid, bronopol, methychloroisothiazolinone, andmethylisothiazolinone. Suitable viscosity modifiers includecarboxymethylcellulose, carboxyethylcellulose, acrylate crosspolymer,and carbomer. Suitable emulsion stabilizers include xanthan gum,glyceryl stearate, and carbomer. If desired, other additives may beincluded to modify the colour or aroma of the topical compositionsdescribed herein.

In a preferred embodiment, mannitol is incorporated to a final weightpercentage between 15 and 90% in a mixture comprising propylene glycol,purified water, isopropyl palmitate, caprylic/capric triglyceride,ceteareth 20, cetearyl alcohol, glyceryl stearate, PEG-100 stearate,dimethicone, octyldodecanol, lecithin, ethylhexylglycerin, andphenoxyethanol.

In other embodiments, mannitol is incorporated into other suitablecarriers known in the art.

The resulting mannitol-based topical composition can be used to treatmany conditions in which cutaneous nerves are involved, including acutepain, chronic pain, autoimmune disorders, itching, eczema, psoriasis,pain and itching associated with mosquito bites, wasp and bee stings,spider bites and burns; neuropathic pain such as diabetic neuropathy,postherpetic neuralgia, osteoarthritis, headaches, neck and back painand tendonitis.

Inventors' own studies suggest the effectiveness of mannitol as atopical pain reliever is distinct from its osmotic effects, and is atleast partly due to down-regulation of the TRPV1 receptor. The TRPV1receptor is present on sensory nerves in the skin and is implicated inneurogenic inflammation, acute pain and chronic pain.

Mannitol has not been used for treating pain through the topical routeof administration. Furthermore, mannitol has not been used via any route(neither subcutaneous nor topical) for the treatment of other conditionsassociated with cutaneous nerves (aside from pain), such as itching andautoimmune disorders.

Equivalent elements can be substituted for the ones set forth above suchthat they perform in substantially the same manner in substantially thesame way for achieving substantially the same result.

What is claimed is:
 1. A topical pain relief composition comprising:between 15 and 90% mannitol by weight; and at least one excipient, theat least one excipient comprising at least one emulsifier; wherein theemulsifier is at least one of the group consisting of a polyethyleneglycol stearate, a glycol stearate, a glyceryl stearate, cetearylalcohol and ceteareth 20, methylcellulose, Cetomacrogol 1000, andlecithin.
 2. The composition of claim 1, wherein the at least oneexcipient further comprises at least one of an organogelator and anemollient.
 3. The composition of claim 1 wherein the topical compositionis one of a cream, gel, lotion, ointment, foam, suppository, and spray.4. The composition of claim 2 further comprising at least one additiveselected from the group consisting of surfactants, penetrationenhancers, preservatives, viscosity modifiers, and emulsion stabilizers.5. The composition of claim 2, wherein the emollient is at least one ofcetostearyl alcohol, cetyl alcohol, isopropyl palmitate, caprylic/caprictriglyceride, PPG-2 myristyl ether propionate, dimethicone, methicone,petrolatum, lanolin, and mineral oil.
 6. The composition of claim 2wherein the organogelator is at least one of 4-tertbutyl-1-arylcyclohecanols derivatives, polymeric (e.g. poly(ethylene glycol),polycarbonate, polyesters, and poly(alkylene), Gemini gelators (e.g.N-lauroyl-L-lysine ethyl ester), Boc-Ala(1)-Aib(2)-β-Ala(3)-OMe(synthetic tripeptide), and low molecular weight gelators (e.g. fattyacids and n-alkanes).
 7. The composition of claim 4 wherein thesurfactant comprises at least one of sodium lauryl sulfate, cetostearylalcohol, ceteareth 12, ceteareth 20, cetearyl alcohol, Cetomacrogol1000, stearic acid, and poloxamers.
 8. The composition of claim 4,wherein the penetration enhancer is propylene glycol.
 9. The compositionof claim 4, wherein the preservative comprises at least one ofmethylparaben, propylparaben, ethylhexylglycerin, phenoxyethanol,chlorocresol, potassium sorbate, sorbic acid, bronopol,methychloroisothiazolinone, and methylisothiazolinone.
 10. Thecomposition of claim 4, wherein the viscosity modifiers are at least oneof carboxymethylcellulose, carboxyethylcellulose, acrylate crosspolymer,and carbomer.
 11. The composition of claim 4, wherein the emulsionstabilizers are at least one of xanthan gum, glyceryl stearate, andcarbomer.
 12. A topical pain relief composition comprising: between 15and 90% mannitol by weight; and at least one excipient, the at least oneexcipient comprising an emollient; the emollient is at least one ofcetostearyl alcohol, cetyl alcohol, isopropyl palmitate, caprylic/caprictriglyceride, PPG-2 myristyl ether propionate, dimethicone, methicone,petrolatum, lanolin, and mineral oil.
 13. The composition of claim 12,wherein the at least one excipient further comprises at least one of anemulsifier, and an organogelator.
 14. The composition of claim 12further comprising at least one additive selected from the groupconsisting of surfactants, penetration enhancers, preservatives,viscosity modifiers, and emulsion stabilizers.
 15. The composition ofclaim 13, wherein the emulsifier is at least one of a polyethyleneglycol stearate, a glycol stearate, a glyceryl stearate, cetearylalcohol and ceteareth 20, methylcellulose, Cetomacrogol 1000, andlecithin.
 16. A topical pain relief composition comprising: between 15and 90% mannitol by weight; and at least one excipient, the at least oneexcipient comprising an organogelator; the organogelator is at least oneof 4-tertbutyl-1-aryl cyclohecanols derivatives, polymeric (e.g.poly(ethylene glycol), polycarbonate, polyesters, and poly(alkylene),Gemini gelators (e.g. N-lauroyl-L-lysine ethyl ester),Boc-Ala(1)-Aib(2)-β-Ala(3)-OMe (synthetic tripeptide), and low molecularweight gelators (e.g. fatty acids and n-alkanes).
 17. The composition ofclaim 16, wherein the at least one excipient further comprises at leastone of an emulsifier and an emollient.
 18. The composition of claim 16further comprising at least one additive selected from the groupconsisting of surfactants, penetration enhancers, preservatives,viscosity modifiers, and emulsion stabilizers.
 19. The composition ofclaim 17, wherein the emulsifier is at least one of a polyethyleneglycol stearate, a glycol stearate, a glyceryl stearate, cetearylalcohol and ceteareth 20, methylcellulose, Cetomacrogol 1000, andlecithin.
 20. The composition of claim 17, wherein the emollient is atleast one of cetostearyl alcohol, cetyl alcohol, isopropyl palmitate,caprylic/capric triglyceride, PPG-2 myristyl ether propionate,dimethicone, methicone, petrolatum, lanolin, and mineral oil.